非白细胞介素-2受体介导的白细胞介素-2外周镇痛作用

PERIPHERAL ANALGESIC EFFECT OF INTERLEUKIN-2 NOT MEDIATED BY INTERLEUKIN-2 RECEPTOR

白细胞介素-2（IL-2）具有中枢及外周神经镇痛作用，但其作用途径不清楚。本实验室曾发现62Glu和126Gln分别是与其受体（IL—2R）的α、γ亚基结合的重要氨基酸，本工作将此两个氨基酸分别突变为Len和Asp，获得62Leu-IL-2和126Asp-IL-2，将两者分别表达并纯化。在大鼠的后足底部注射纯品。采用热板法，测定大鼠的痛阈。结果发现：突变体虽已丧失其免疫功能，但不丧失其对大鼠的镇痛作用，而IL—2的镇痛作用可被阿片肽受体拮抗剂纳络酮（Naloxone）阻断，说明IL—2的外周镇痛作用很可能不是由IL—2R所介导，其作用机理可能与阿片受体有关。

It was found that interleukin-2 (IL-2) has central and peripheral analgesic effect, and we alsofound that 62Gln and 126Gln in IL-2 molecule are crucial for binding with α and γ subunits of IL-2 receptor (IL-2R) respectively. We purified mutant protein (62Leu-IL-2 and 126Asp-IL-2) whose immuno-activitydecreaded significantly or lost completely. However, injecting subcutaneously the mutated IL-2 proteins into thereceptive field of rat's hindpaw that was stimulated by noxious heating, we found that both 62Len-IL-2 and 126 AspIL-2 significantly increased the pain threshold (PT) of rats. Futhermore the analgesic effect of IL-2 could beblocked by naloxone which is an antagonist of opioid receptors. The above data seems to indicate that IL-2R mightnot involve in the peripheral analgesic effect, and that the analgesic effect of IL--2 might be related to opioidreceptors.